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Nephrology was a European monopoly lasting 1500 years. Any progress, any change, any new thing was European. I will go very quickly through the history of nephrology which will only take me 2 minutes to come to the heart of the matter.

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So, it’s only when Galenus who was a Roman, he treated the gladiators but he was the first physiologist, he found that the kidneys were producing the urine. It looks very strange to mention that now but he proved really by physiological experiments the origin of urine and he also did a lot of fluid balance experiments. This is really the renal physiology of the early times since Galenus.

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Then darkness came over Europe lasting thousands of years, 1400 years nothing happened because the Catholic Church was controlling everything. It is thanks to a Flemish man, a young man who during Renaissance and I remember the date 1543, he wrote a book, a masterpiece in physiology and anatomy. It was the first printed book and was still maintained for 300 years in the teaching of anatomy and physiology. This was thanks to the fact that the Renaissance was coming and for the first time people could think very freely about several scientific subjects.

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The remarkable thing is that 1543 was the year that Mr Copernicus died but his book of 1543: De Revolutionibus Orbium Coelestium, which is the first time that the sun was the centre of the world and not the earth and you will remember that later on the Catholic Church combat that very strongly and even burned some people later on, those who dared to think that the earth was not the centre of the world. So 1543 was a very important date.

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Harvey, of course, is important and helped the physiology of the kidney to move forward because he discovered the circulation and of course, without circulation you can’t do anything.

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Malpighi described beautifully with this microscope from Dutch facture this wonderful memorable glance round like eggs of fish which were the glomeruli and this was the first time that in science in the 17th century, 1666 that the glomeruli were described.

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Then after Darwin who was a masterpiece in thinking

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came the people who for the first time, still Europeans and English, described the whole nephron in a beautiful graph in 1856 on the Physiological Anatomy and Physiology of Man.

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He was supported by a German, Jacob Henle who defined the thing and that was still all European.

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And then America came on the scene and very quickly was, I’m not saying overwhelming, but dominating the scene in renal physiology and pathophysiology with Homer Smith who did a wonderful work on renal physiology.

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And then a whole generation of Americans, Robert Pitts and many others. It was European, it is still European and American and I hope but now belongs to the world.

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But before I go into detail of the renal science I want to show you how the overall biomedicine is behaving. This is basic science and analysis of the best producing countries from 1991 until 2000. The point is that you see here the orange bars are 1991 and the blue ones are 2000 figures and you see the United States goes down from almost 70% of production in basic science to 53%. Most of our other players are European countries and already China is on board and Australia is doing rather well and Canada is also doing very well. And some of them are going up like here Germany, Japan, the Netherlands, Sweden and here you see Denmark and China are coming up in the field of basic science which is the production found in cell nature you know the big journals where you can really get a little bit if you publish one or two times in Nature your career is done.

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Let’s go to the clinical science. Here you see the most important journals in medicine, in general medicine. It’s not especially renal medicine. Again, the United States is going down from 60-52%. The United Kingdom is not doing so badly from 13-17%, it’s the most productive country at least in general clinical medicine from Europe and the other countries. Again, most of them are European except Japan, of course, Australia and Canada again.

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Let’s now go to nephrology and make a picture of what we do and are we really well performing? The first point is that this is the number of randomised controlled trials and as you know, a randomised controlled trial is a trial which you will use for evidence based medicine. It’s a classic now accepted everywhere as a very important reference. You see that nephrology is doing rather badly. We are on the bottom of the list in the production of randomised controlled clinical trials from all disciplines in medicine. Among them there are small ones, you can argue that nephrology is a small discipline but there are also other small disciplines like endocrinology and haematology. Obviously, gastroenterology and cardiovascular disease are on the top but among the small ones we are among the least producing number of randomised clinical trials.

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Even if you look to the number, of the percentage of randomised clinical trials versus total citation in nephrology we still are not doing very well, we are among the third least best.

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And to give you more interest for us in what is the most weak part of our clinical trials it is not transplantation, it is not dialysis, these are doing rather well but it is for example, glomerulonephritis. There are not enough well done prospective randomised controlled trials in the very important renal disease, namely glomerulonephritis.

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So in summary and on this very important aspect of randomised clinical trials, the number of RCTs published in Nephrology from 1966-2002 is fewer than any other speciality of internal medicine. The proportion of all citations which are RCTs related is the third lowest. The increase in both these items is at a lower rate compared to other specialities, so we have not been improving over the years. There has been no increase observed over the past 5 years. Glomerulonephritis is an outlier with a very low number of randomised clinical trials. I want to cite here something which I find extremely important. I am now investigating and I still don’t have the results but I have results from my own country. The non-industry driven research in Western Europe is almost becoming negligible. 95% of all the research done in our discipline is industry driven and I think this is not a good evolution. There must be a balance between the industry driven and the investigator driven research. In my country, I can give you these preliminary results and I’m working on it in other countries, 95% of all the research is industry driven and that’s much too much.

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So, we have to think about that as a very important threat that an industry will never do particular trials because they’re not interested in them. So how can we improve? The quality is low and has not improved over the past 30 years. The main reason is the unclear allocation concealment. There is no allocation concealment in a lot of trials. There is a lack of reported blinding of outcome assessors and the failure to perform intention-to-treat analysis is very frequent in a substantial number of trials that have been published over the years.

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So we should use standard guidelines and checklists of trial reporting published and this is available on the internet and is now fairly easy to access. This is involving experts in trial design and reporting. Multicentre collaboration has to be done much more frequently and larger and simple trials should be done in nephrology.

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I will now come to the clinical researcher.

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So clinical research is difficult, it’s more difficult compared to the basic one and the reasons are the following. The probability of success is less. You have much more easy success by cell culture and submitting the cells or the rats to a certain dose of something then you have your patients who are much more complicated. The pace is much slower, the salaries are conflicting with practicing medicine all over Europe. Practising medical doctors in general and nephrologists particularly have completely other salaries than those who have a research career There’s a lower chance for funding, if you have to be funded for clinical, pure clinical research, patient related the chance is low. The demands for clinical income from all our hospitals is so high that there is insufficient protected time of the clinician who wants to do something. There is isolation of young clinicians for active research and there is a dramatic loss of scientist role model and experienced mentors. So the two way interaction between bench and bedside is dramatically weakened.

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So how can we improve that? We have to link clinical medicine and basic research much more which in the past was occurring more frequently. Save the MD, PhD species form extinction. I hope one day we will not be able to produce in Europe the same that is now produced in the United States that the MD and PhD is almost a disappearing species.

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The whole science is now produced by the PhDs. I’m a MD PhD, I know very well what that means. We need doctors in the lab which are the counter-interacting people talking everyday to the PhDs on how a clinical question can be implemented into rats and cells etc and not the reverse. So I hope we will not be able to produce such a slide in Europe in a few years.

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So we have to create research careers with adequate funding, clear career paths because we don’t have that in Europe a lot. More public confidence, the public is not more confident anymore in the producing of the scientific results. There’s an organisation in the United Kingdom made by the government that will now try to translate the science of clinical medicine into the public. We have to implement new medical developments and therapies. The European framework programs. I have participated in several European framework programs, FB6, 5, 7, etc. We should fund hypotheses-driven research, behave less bureaucratic and avoid duplication which is seldom the case in Europe. We should get top industrial R and D investment in Europe which is leaving Europe for the moment and we should also identify and expose research fraud in industry-funded research.

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I’m happy to see that ERA-EDTA over the years has started at least to improve the situation, trying to improve the situation by their fellowship programmes which started recently and here we have the figures and also by their clinical and research courses of epidemiology forefront and specifically of course, the educational programmes. But they have no funded until now randomised clinical trials which I think is one of the goals of the ERA-EDTA. I’ll come to that in my conclusions.

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I will now give you the results of a personal study I performed in the last 3 months. I have analysed the Journal of the American Society of Nephrology, in Kidney International and in the American Journal of Kidney Disease which are the three best journals in nephrology and I did that over the last 2000 and 2006 and 2002- 2006 for Kidney because of a question of time. So I first divided it between Europe, United States, Canada, Japan and Australia. Here is the Journal of the American Society of Nephrology and on the top the Kidney International and American Journal of Kidney Disease. As you can see, we are not leaders in the field. Leaders in the field are United States, Canada and Australia. You are number 4 or 5, you are comparable to Japan concerning that I expressed this number as the number of papers per million inhabitants to normalise for the surface and the population, of course, otherwise you have –. So in Europe we produced 2.2 papers of Kidney International over that period of time per million inhabitants. So here clearly you see that overall Europe is certainly not leading anymore in the let’s say clinical research of basic research in nephrology, in other words in translational nephrology.

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Let’s now ventilate that over the different countries in Europe. All the countries mentioned here are all countries who have at least more than one paper per million inhabitants over the years in JASN. So, JASN was analysed over a time period lasting from 2000-2006 and the mean in Europe as I said is 2.2. You see here in Europe the difference is dramatic because all that is normalised. The Netherlands are doing very well, 7.8 papers per million inhabitants over that period of time and you see the difference going down until 1.2 for Spain. So this is a striking difference and it is normalised for the number of inhabitants of that country. So you can compare, you can always argue about this way of presenting that but it’s the best way and the most acceptable and feasible way. If you look, for example, here at the United States is here and Japan is here. This is the Journal of the American Society of Nephrology.

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The second journal is Kidney International and again, the striking point is that the Netherlands are again, number one far out followed by Belgium and interestingly in the top five in Europe they are all small countries with number of inhabitants below 20 million except for Australia which is doing very well. So it’s nice interesting observation and it’s also the case in JASN that most countries (not all) with a low number of inhabitants have the highest score per million of inhabitants.

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Finally, you see here the American Journal of Kidney Disease and here Austria is leading and again the Netherlands is not doing very badly. So overall what’s come out of this analysis is that the small countries are not doing so badly and one of them, the Netherlands is doing very well, much better than any other one, and the differences are substantial.

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What are the reasons for that? I have a lot of friends in the Netherlands and I know the system rather well. In the Netherlands there are 165 nephrologists. 30% of them are in university hospitals and until recently all the nephrologists had to have a PhD even if they go to private medicine, they have to defend a thesis before a university jury. Not only that the theses are excellent because they have to contain 4 papers as first author in peer reviewed journals with a high impact factor among the 6 best journals in nephrology. This is not easy to obtain, if you look to the general theses in the world and I can tell you I have visited many countries in the world and assisted many defences of theses, this is among the most severe number of qualifications before you can graduate for a thesis. In addition, the Netherlands has a research funding like many of us, they have the National Council for fundamental and applied research. They have the faculties with post doctoral – like we have in many countries,. Some of their hospitals have a budget which is becoming exceptional in Europe for clinical research but they have something special.

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They have the ‘Nierstichting’. I will give you some information about that. This is the fund, the Netherlands Kidney Foundation which is based on four professionals who all day all year long organise collections, mailing actions, legacies, gifts etc and they collected in 2006 15 million euros. Of these 15 million euros, 75% was spent in research and the ventilation of that research is shown here, it is prevention, biomedical research, social policy patient care, children with kidney disease etc. This is from the webpage of this impressive association and efficient initiative which has been doing this for more than 15 years. The budget here of 2006 is not exceptional, it’s an average. So this makes the power of this country which not only has gifted people, well trained people, but also uses them in the appropriate way and also use the appropriate funding.

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When I explained that to one of my many friends in the Netherlands, one of those friends told me the reason is very simple, we are Calvinists and we are entrepreneurs and this makes all together that it is the success of our history.

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But I will end by telling you that if we used all the qualifications we have in Europe, be it the cultural heritage, and the courage of the Greeks

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or the poetry and ecology of the Danish

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or the precision and the purity of the Swiss

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or the balance and the talent of the Austrians,

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the no nonsense and compromise of the Belgians.

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The sense of excellence and harmony of the Swedish.

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The tradition and the tenacity of the British.

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The creativity and versatility of the Italians.

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The gründlichkeit and commitment of the Germans.

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The revolutionary thinking and freedom sense of the Polish.

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The fantasy and authenticity of the Spanish.

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The audacity and the lyrism of the Portuguese.

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The pride and immensity of the Russians

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and the logical thinking and sensuality of the French,

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I think we should make a strong European research network

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and in conclusion the bench to bedside medicine in Europe is not optimal. There’s room for improvement and we should know that, we should know where we stand in the world of science, it’s not so impressive. Second the performance in different countries in Europe is strikingly different. We can learn a lot from the Dutch model. The role of the EDTA-RCT could be that randomised clinical trials should be done and organised by the European Organisation like our organisation and finally, collaboration, exchange, confidence and trust are the most important things of research. I thank you for your attention.

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Chairman: My most sincere congratulations for this really excellent presentation. I really have learned a lot. This presentation is open for questions. Any questions or comments? Well, you have shown the results Doctor De Broe in three journals, American journals. We have a problem in Europe with the language that is an additional limitation to publish in these journals. Did you review also in addition the NDT articles published in the European journals?

Prof. De Broe: I have not done it yet because first of all, it’s time consuming, it takes a lot of time and I only used journals, I never used reviews, I never used letters to the editor. All that was cancelled, it was only the original papers in the journals and I thought, I was the Dean of the faculty for several years and I introduced in my university that the people had to publish in whatever discipline in the 6 best journals of the discipline. I think it’s a good goal to go and to stimulate people to do the best they can and as you can see it pays off if you look to the Netherlands system and a condition because everybody speaks English and even in several journals you can send out the journal in and I can tell you I am an associate of Kidney International and we have a system where we try to correct manuscripts which are from people who are not used to using the English language. So the English language cannot be a barrier. I’m pretty sure but the second message is we have to try by all means to produce maybe less number of journals and a number of very good journals is much better than the plethora of journals we have nowadays. Thank you.

Question: Can I make a suggestion. I’m the only council member here, the president of the next congress in Stockholm is here. How could we make your talk now with the results of the rest of the council could I communicate this?

Prof. De Broe: I accept the invitation if I can do it again next year because I will have much more data on that because for me it’s becoming an obsession that quality in research is extremely important, it is not the number first which is important, it’s the quality and the second is and I have this data I don’t have it yet but I have started to collect it. I am collecting data on the industry-driven research versus investigator-driven research and this is a drama in Western Europe and all over the world. We cannot do the exact clinical trials with the questions that have to be asked will never be supported by industries. I give an example if you want to know if the two new non-calcium containing phosphate binders are comparable better or whatever the industry will never support that, we have to do that and I’ll give you several other examples of that. We get a much more freedom from the industry. I have been working with industries for more than 20 years and I have a very good relationship but it has to be open, very clear, straightforward and there must be financial possibilities to do in our own autonomy particular clinical trials.

Question: -- Stockholm thank you for your very thought provoking lecture. The performance of the Dutch is, of course, impressive and this foundation is interesting. How did it start?

Prof. De Broe: The Dutch are, as I said, Calvinistic, entrepreneurs and extremely pragmatic. They have the same egomaniacs, the same political questions etc like we all have in our countries but once the benefit of everybody is at stake, they can come together. That’s one of the secrets of the Dutch, if things are at stake they can really come together and write protocols and do the job altogether and they organise themselves very well. They started with that 15 years ago, very small and after 5 years it was such a success that as you have seen it’s almost 10 times the budget of the ERA spending on research which is very impressive.

Chairman: So let’s thank again Doctor De Broe for your excellent preparation and presentation.